McSherry C K, Morrissey K P, Swarm R L, May P S, Niemann W H, Glenn F
Ann Surg. 1976 Oct;184(4):490-9. doi: 10.1097/00000658-197610000-00012.
The prolonged feeding of chenodeoxycholic acid produces hepatic injury in both pregnant and non-pregnant baboons. CDC feeding does not adversely affect ovarina function and no teratogenic effects of this bile acid were noted in 16 live birth and two stillborn progeny of CDC fed animals. However, 10 of the 16 live birth neonates and one stillborn had focal hepatic lesions histologically similar to those observed in the adult animals. In addition one neonate had gross hepatic necrosis. The severity of the liver damage was related to the content of lithocholic acid in the bile of both the neonates and their mothers. Experiments with 14C-chenodeoxycholic and 14C-lithocholic acid demonstrate that the lithocholate in the enterohepatic circulation of the neonate is derived from the CDC fed to the pregnant adult. In the gallbladder bile of the neonate most, but not all, of the lithocholate is conjugated but unsulfated. Both newborn and adult baboons sulfate lithocholic acid but to an extent less than that reported for man. Less efficient sulfation of lithocholic acid in the baboon may exaggerate the toxicity of CDC feeding in this species compared to man. Nevertheless, the potential for adverse effects on the fetal liver must be recognized as a risk associated with the use of chenodeoxycholic acid in women of child-bearing age.
长期给怀孕和未怀孕的狒狒喂食鹅去氧胆酸会导致肝损伤。喂食鹅去氧胆酸不会对卵巢功能产生不利影响，在喂食鹅去氧胆酸的动物所生的16只活产幼崽和2只死产幼崽中未发现这种胆汁酸有任何致畸作用。然而，16只活产新生儿中有10只以及1只死产儿有局灶性肝损伤，其组织学特征与成年动物中观察到的相似。此外，有1只新生儿有明显的肝坏死。肝损伤的严重程度与新生儿及其母亲胆汁中石胆酸的含量有关。用14C-鹅去氧胆酸和14C-石胆酸进行的实验表明，新生儿肠肝循环中的石胆酸盐来源于给怀孕成年动物喂食的鹅去氧胆酸。在新生儿的胆囊胆汁中，大部分（但不是全部）石胆酸盐是结合型但未硫酸化的。新生狒狒和成年狒狒都会对石胆酸进行硫酸化，但程度低于人类报道的水平。与人类相比，狒狒中石胆酸硫酸化效率较低可能会加剧喂食鹅去氧胆酸对该物种的毒性。尽管如此，必须认识到对胎儿肝脏产生不良影响的可能性是育龄妇女使用鹅去氧胆酸所带来的风险。
